Submissions for variant NM_000527.5(LDLR):c.1413A>G (p.Arg471=)

gnomAD frequency: 0.65878  dbSNP: rs5930

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000182337	SCV000269223	benign	not specified	2016-02-09	criteria provided, single submitter	clinical testing	Arg471Arg in exon 10 of LDLR: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 38.4% (3301/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5930).
LDLR-LOVD, British Heart Foundation	RCV000237328	SCV000295415	benign	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
PreventionGenetics, part of Exact Sciences	RCV000182337	SCV000304685	benign	not specified		criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000237328	SCV000322950	benign	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research	20 Hmz + 37 Htz / 92 non-FH individuals; MAF = 29,7% in 86 Spanish healthy individuals
Illumina Laboratory Services, Illumina	RCV000237328	SCV000410533	benign	Hypercholesterolemia, familial, 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000237328	SCV000689760	benign	Hypercholesterolemia, familial, 1	2017-05-30	criteria provided, single submitter	clinical testing
Department of Human Genetics, Laborarztpraxis Dres. Walther, Weindel und Kollegen	RCV000237328	SCV000987006	benign	Hypercholesterolemia, familial, 1	2018-05-23	criteria provided, single submitter	clinical testing	Due to the increased occurrence of the mutation (>= 5%), this variant is classified as benign.
Invitae	RCV001275279	SCV001729839	benign	Familial hypercholesterolemia	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000237328	SCV001737998	benign	Hypercholesterolemia, familial, 1	2021-06-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812170	SCV002049834	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002390458	SCV002700361	benign	Cardiovascular phenotype	2016-03-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000237328	SCV000606417	benign	Hypercholesterolemia, familial, 1		no assertion criteria provided	research
Natera, Inc.	RCV001275279	SCV001460277	benign	Familial hypercholesterolemia	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000182337	SCV001920704	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000182337	SCV001963241	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV001275279	SCV003836763	benign	Familial hypercholesterolemia	2023-02-09	no assertion criteria provided	clinical testing